Clinical Characteristics and Outcomes of Extranodal Stage I Diffuse Large B Cell Lymphoma in The Rituximab-Era.

This retrospective study aimed to better define the characteristics and outcomes of extranodal stage I DLBCL in the rituximab era. Patients diagnosed with stage I DLBCL from 2001-2015 treated with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) or R-CHOP-like regimens with or without radiation (RT) were included. We identified 1955 patients with newly diagnosed DLBCL, of whom 341 had stage I and were eligible for this analysis. Extranodal presentation was observed in 224 (66%) patients, while 117 (34%) had nodal involvement. The most common extranodal sites were bone 21%; stomach 19%; testis 9%; intestine 8%; breast 8%. Overall, 69% extranodal and 68% nodal patients received RT. Median follow-up was 5.5 years (interquartile range 4.3-8.2). 10-year overall survival (OS) and disease-free survival were 77% (95% CI 67%, 83%) and 77% (95% CI 68%, 85%). In the multivariable analyses, extranodal involvement was associated with worse OS (HR 3.44, 95% CI 1.05, 11.30) and progression-free survival (PFS) (HR 3.25, 95% CI 1.08, 9.72) compared to nodal. Consolidation RT was associated with better OS (HR, 0.26, 95% CI 0.12, 0.49) and PFS (HR, 0.35, 95% CI 0.18, 0.69) in the extranodal population; however, the benefit was no longer observed in patients with PET negative at the end of immunochemotherapy. Relapses occurred usually late (median 37 months) and the most common sites were the lymph nodes (31%) and the central nervous system (27%). Extranodal stage I DLBCL had a worse outcome than nodal. End of immunochemotherapy PET results may help select extranodal patients for consolidation RT.

[1]  A. Rosenwald,et al.  Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial , 2019, The Lancet.

[2]  Sonali M. Smith,et al.  PET-Directed Therapy for Patients with Limited-Stage Diffuse Large B-Cell Lymphoma - Results of Intergroup Nctn Study S1001 , 2019, Blood.

[3]  D. Scott,et al.  Long-Term Follow-up of a PET-Guided Approach to Treatment of Limited-Stage Diffuse Large B-Cell Lymphoma (DLBCL) in British Columbia (BC) , 2019, Blood.

[4]  M. Ziepert,et al.  Radiotherapy (RT) to bulky (B) and extralymphatic (E) disease in combination with 6xR-CHOP-14 or R-CHOP-21 in young good-prognosis DLBCL patients: Results of the 2x2 randomized UNFOLDER trial of the DSHNHL/GLA. , 2018 .

[5]  R. Houot,et al.  R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma. , 2018, Blood.

[6]  H. Kluin-Nelemans,et al.  Relapse in stage I(E) diffuse large B‐cell lymphoma , 2017, Hematological oncology.

[7]  Sonali M. Smith,et al.  Continued Risk of Relapse Independent of Treatment Modality in Limited-Stage Diffuse Large B-Cell Lymphoma: Final and Long-Term Analysis of Southwest Oncology Group Study S8736. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  J. Byrd,et al.  Diffuse Large B-Cell Lymphoma Version 1.2016. , 2016, Journal of the National Comprehensive Cancer Network : JNCCN.

[9]  A. Zelenetz,et al.  Excellent outcomes and lack of prognostic impact of cell of origin for localized diffuse large B‐cell lymphoma in the rituximab era , 2015, British journal of haematology.

[10]  Lane F Burgette,et al.  A tutorial on propensity score estimation for multiple treatments using generalized boosted models , 2013, Statistics in medicine.

[11]  L. Sehn Chemotherapy Alone for Localized Diffuse Large B-Cell Lymphoma , 2012, Cancer journal.

[12]  A. López-Guillermo,et al.  First-line treatment for primary testicular diffuse large B-cell lymphoma with rituximab-CHOP, CNS prophylaxis, and contralateral testis irradiation: final results of an international phase II trial. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  B. Coiffier,et al.  Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. , 2010, Blood.

[14]  Christine F. Wogan,et al.  Benefit of consolidative radiation therapy in patients with diffuse large B-cell lymphoma treated with R-CHOP chemotherapy. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  R. Gascoyne,et al.  Prognostic implications of extranodal involvement in patients with diffuse large B-cell lymphoma treated with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone , 2010, Leukemia & lymphoma.

[16]  P. Gaulard,et al.  Primary breast non‐Hodgkin's lymphoma: A large single center study of initial characteristics, natural history, and prognostic factors , 2009, American journal of hematology.

[17]  L. Rimsza,et al.  Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  T. Molina,et al.  CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: a study by the Groupe d'Etude des Lymphomes de l'Adulte. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  E. Giné,et al.  Diffuse large B-cell lymphoma: clinical and biological characterization and outcome according to the nodal or extranodal primary origin. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  T. Molina,et al.  ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. , 2005, The New England journal of medicine.

[21]  B. Christensen,et al.  Diffuse large B‐cell lymphoma: clinical implications of extranodal versus nodal presentation – a population‐based study of 1575 cases , 2004, British journal of haematology.

[22]  B. E. C. Oiffier,et al.  CHOP Chemotherapy plus Rituximab Compared with CHOP Alone in Elderly Patients with Diffuse Large-B-Cell Lymphoma , 2002 .

[23]  E. Noordijk,et al.  Treatment, patterns of failure, and survival of patients with Stage I nodal and extranodal non‐Hodgkin's lymphomas, according to data in the population‐based registry of the comprehensive cancer centre west , 1998, Cancer.

[24]  R. Fisher,et al.  Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. , 1998, The New England journal of medicine.

[25]  김진석 Matched-pair analysis comparing the outcomes of primary breast and nodal diffuse large B-cell lymphoma in patients treated with rituximab plus chemotherapy. , 2012 .

[26]  L. Staudt,et al.  Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. , 2004, Blood.

[27]  S. Cessie,et al.  Primary extranodal non-Hodgkin's lymphoma (NHL): the impact of alternative definitions tested in the Comprehensive Cancer Centre West population-based NHL registry. , 2003, Annals of oncology : official journal of the European Society for Medical Oncology.